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1.
  • Lundälv, Jörgen, 1966 (författare)
  • Dela ut gratis reflexer till folket
  • 2008
  • Ingår i: Debattartikel i Karlskoga Tidning den 17 november 2008..
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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2.
  • Waraky, Ahmed (författare)
  • Insulin-like growth factor 1 receptor, novel functions and future possibilities
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Insulin like growth factor-1 receptor (IGF-1R) has been shown to be important for cancer cell growth and survival, and is often overexpressed in malignant and premalignant tissues. Ligand binding to IGF-1R induces transphosphorylation and activation of the receptor, leading to subsequent activation of the phosphatidyl inositol-3 kinase (PI3K), the mitogen-activated protein kinase (MAPK) and the 14-3-3 pathways. Most of these pathways are shared by other receptor tyrosine kinases. Inhibition of these pathways using specific IGF-1R antibodies has, however, failed in large trials on cancer patients. This opens the possibilities for alternative signaling pathways. Recently, IGF-1R was shown to be SUMOylated and translocated to the cell nucleus. In the nucleus it binds to enhancer-like regions, and regulates expression of genes including CCND1 and AXIN2, and phosphorylates Histone3. The expression of nuclear IGF-1R has also been linked to increased cell growth and aggressive phenotype in cancer. In paper I the effects of picropodophyllin (PPP), an inhibitor of IGF-1R, on cell cycle progression were studied. Previous studies have indicated that PPP treated cells arrest in G2/M. We found that PPP induced G2/M arrest through interfering with microtubule dynamics causing prolonged mitotic arrest and mitotic catastrophe in an IGF-1R independent manner. This mechanism of PPP may contribute to its efficacy in treatment of cancer patients. In paper II the roles of SUMOylated IGF-1R in regulating cell proliferation and cell cycle progression were investigated. We provided evidence that SUMOylation of IGF-1R increases G1/S phase transition through inducing expression of cyclins (D, A and B) and upregulating CDK2. Cells expressing SUMOylated IGF-1R also proliferated faster and formed more colonies in soft agar compared to cells expressing IGF1R with mutated SUMO-binding sites. In paper III we investigated potential binding partners to nuclear IGF-1R in human embryonic stem cells (hESC). We found that nuclear IGF-1R associates with PCNA and phosphorylates it, not only in hESCs but also in other cell types. The nuclear IGF-1R-induced PCNA phosphorylation was followed by ubiquitination of PCNA, probably through DNA damage tolerance (DDT)-dependent E2/E3 ligases (e.g. Rad18 and UBC13). Our data suggest that IGF-1R may contribute to activation of DDT, as externally induced DNA damage in IGF-1R negative cells led to G1 cell cycle arrest and larger S-phase fork stalling compared to cells expressing IGF-1R. In summary, the achieved results may contribute in understanding the complexity of IGF-1R’s roles in cell growth and maintenance of genome stability, as well as the shown mitotic block induced by PPP may be a mechanism that favors anti-IGF-1R treatment in cancer.
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3.
  • Wange, Niklas, et al. (författare)
  • Bleeding risk in patients with venous thromboembolic events treated with new oral anticoagulants
  • 2021
  • Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer. - 0929-5305 .- 1573-742X. ; 52:1, s. 315-323
  • Tidskriftsartikel (refereegranskat)abstract
    • New oral anticoagulants (NOACs) is the preferred treatment in secondary prophylaxis of venous thromboembolic events (VTE). The aim of this study was to investigate possible risk factors associated with major bleeding in VTE-patients treated with NOACs. In this retrospective register-based study we screened the Swedish anticoagulation register Auricula (during 2012.01.01-2017.12.31) to find patients and used other national registers for outcomes. Primary endpoint was major bleeding defined as bleeding leading to hospital care. Multivariate Cox-regression analysis was used to reveal risk factors. 18 219 patients with NOAC due to VTE were included. 85.6% had their first VTE, mean age was 69.4 years and median follow-up time was 183 days. The most common NOAC was rivaroxaban (54.8%), followed by apixaban (42.0%), dabigatran (3.2%) and edoxaban (0.1%). The rate of major bleeding was 6.62 (95% CI 6.19-7.06) per 100 treatment years in all patients and 11.27 (CI 9.96-12.57) in patients above 80 years of age. Statistically independent risk factors associated with major bleeding were age (normalized HR 1.38, CI 1.27-1.50), earlier major bleeding (HR 1.58, Cl 1.09-2.30), COPD (HR 1.28, CI 1.04-1.60) and previous stroke (HR 1.28, Cl 1.03-1.58) or transient ischemic attack (TIA) (HR 1.33, Cl 1.01-1.76). Prior warfarin treatment was protective (HR 0.67, CI 0.58-0.78). This real world cohort shows a high bleeding rate especially among the elderly and in patients with previous major bleeding, COPD and previous stroke or TIA. This should be considered when deciding on treatment duration and NOAC dose in these patients.
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5.
  • Carroll, DC, et al. (författare)
  • Active manipulation of the spatial energy distribution of laser-accelerated proton beams
  • 2007
  • Ingår i: Physical Review E (Statistical, Nonlinear, and Soft Matter Physics). - 1539-3755. ; 76:065401(R), s. 1-065401
  • Tidskriftsartikel (refereegranskat)abstract
    • The spatial energy distributions of beams of protons accelerated by ultrahigh intensity (>10^19 W/cm2) picosecond laser pulse interactions with thin foil targets are investigated. Using separate, low intensity (<10^13 W/cm2) nanosecond laser pulses, focused onto the front surface of the target foil prior to the arrival of the high intensity pulse, it is demonstrated that the proton beam profile can be actively manipulated. In particular, results obtained with an annular intensity distribution at the focus of the low intensity beam are presented, showing smooth proton beams with a sharp circular boundary at all energies, which represents a significant improvement in the beam quality compared to irradiation with the picosecond beam alone.
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7.
  • Tasmin, Saira, et al. (författare)
  • Effects of Short-term Exposure to Ambient Particulate Matter on the Lung Function of School Children in Dhaka, Bangladesh
  • 2019
  • Ingår i: Epidemiology. - : Wolters Kluwer. - 1044-3983 .- 1531-5487. ; 30:Suppl 1, s. S15-S23
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Ambient particulate pollution may adversely affect children's lung function. However, evidence on this association remains scarce in Asia despite this region having the greatest burden of disease due to air pollution.OBJECTIVES: To investigate the effect of short-term exposure to ambient particulate matter (PM) on the lung function of school children in Dhaka city, Bangladesh. The possible seasonal modification of this association was also examined.METHODS: A panel of 315 school children who were 9-16 years of age were recruited from three schools in and around Dhaka. Lung function was assessed using a spirometry test during the cool and warm seasons in 2013, yielding six measurements per child. Daily PM data were retrieved from nearby air monitoring stations. Linear mixed effects models were used to examine associations. Seasonal modification was examined by stratification.RESULTS: An inverse association was observed for the lung function parameters with PM2.5; peak expiratory flow (PEF) and forced expiratory volume within 1 second (FEV1) decreased with increasing PM2.5. The percent deviation from the personal median was -4.19% [95% confidence interval (CI): -5.72, -2.66] for PEF and -2.05% (95% CI: -2.92, -1.18) for FEV1 for a 20 µg/m increase in PM2.5 on the previous day. Results for PM10 were less consistent. The estimated effects of PM on lung functions were generally greater in the warm season.CONCLUSIONS: Short-term exposure to PM is associated with worse lung function in children living in highly polluted settings, with the strength of these adverse PM effects varying by season.
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8.
  • Isoz, Oscar, et al. (författare)
  • Interference detection and localization in GPS L1 band
  • 2010
  • Ingår i: Proceedings of the 2010 International Technical Meeting of The Institute of Navigation. - Manassas, VA : Institute of Navigation, The. - 9781617381157 ; , s. 925-929
  • Konferensbidrag (refereegranskat)abstract
    • The GNSS signals are very weak and therefore sensitive to interference. Since the usage of GNSS based services continues to increase, there is a need to develop a cost effective method to detect and localize interference sources. In this paper one such system will be presented. The system uses independent front ends that collects raw IF data. After the collection is done, the files are synchronized in time and frequency so that they can be cross correlated and the time difference of arrival of the interference signal is estimated. This paper will present the initial results from a test in May 2009 where the four stations were deployed and exposed to interference. It will be shown that the system is capable of both detection and localization of wide band interference.
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9.
  • Larsson, Charlotta, et al. (författare)
  • Anal incontinence after caesarean and vaginal delivery in Sweden : a national population-based study
  • 2019
  • Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 393:10177, s. 1233-1239
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Elective caesarean delivery is increasing rapidly in many countries, and one of the reasons might be that caesarean delivery is widely believed to protect against pelvic floor disorders, including anal incontinence. Previous studies on this issue have been small and with conflicting results. The aim of present study was to compare the risk of developing anal incontinence in women who had a caesarean delivery, in those who had a vaginal delivery, and in two age-matched control groups (nulliparous women and men).Methods: In this observational population-based study, we included all women in the Swedish Medical Birth Register who gave birth by caesarean delivery or vaginal delivery during 1973-2015 in Sweden and were diagnosed with anal incontinence according to ICD 8-10 in the Swedish National Patient Register during 2001-15. Exclusion criteria were multiple birth delivery, mixed vaginal and caesarean delivery, and four or more deliveries. We compared the diagnosis of anal incontinence between women previously delivered solely by caesarean delivery and those who solely had delivered vaginally. We also compared it with two age-matched control groups of nulliparous women and men from the Swedish Total Population Register. Finally, we analysed risk factors for anal incontinence in the caesarean delivery and vaginal delivery groups.Findings: 3 755 110 individuals were included in the study. Between 1973 and 2015, 185 219 women had a caesarean delivery only and 1 400 935 delivered vaginally only. 416 (0.22 %) of the 185 219 women in the caesarean delivery group were diagnosed with anal incontinence compared with 5171 (0.37%) of 1 400 935 women in the vaginal delivery group. The odds ratio (OR) for being diagnosed with anal incontinence after vaginal delivery compared with caesarean delivery was 1 center dot 65 (95% CI 1 center dot 49-1 center dot 82; p<0.0001). When the combination vaginal delivery and caesarean delivery was compared with the nulliparous control group, the OR of being diagnosed with anal incontinence was 2 center dot 05 (1 center dot 92-2 center dot 19; p<0.0001). For the nulliparous women compared with men, the OR for anal incontinence was 1 center dot 89 (1 center dot 75-2 center dot 05; p<0.0001). The strongest risk factors for anal incontinence after vaginal delivery were high maternal age, high birthweight of the child, and instrumental delivery. The only risk factor for anal incontinence after caesarean delivery was maternal age.Interpretation: The risk of developing anal incontinence increases after pregnancy and delivery. Women with known risk factors for anal incontinence should perhaps be offered a more qualified post-partum examination to enable early intervention in case of injury. Further knowledge for optimal management are needed. Copyright (c) 2019 Elsevier Ltd. All rights reserved.
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10.
  • Larsson, Per, et al. (författare)
  • Heavy metals and stable isotopes in a benthic omnivore in a trophic gradient of lakes
  • 2007
  • Ingår i: Environmental Science & Technology. - : American Chemical Society (ACS). - 1520-5851 .- 0013-936X. ; 41:17, s. 5973-5979
  • Tidskriftsartikel (refereegranskat)abstract
    • Heavy metals (Cd, Hg, and Pb) and stable isotopes (N-15, C-13) in crayfish (Pacifastacus leniusculus) were studied in a trophic gradient of lakes (N = 19) in southern Sweden. Trophic indicators of the lakes as total phosphorus (tot-P) varied from 5 to 93 mu g/L. The examined lakes had no known point sources of heavy metals, but the catchment areas varied from mainly forested to agricultural land. Cd and Hg in crayfish were affected by the trophic status of the lakes, showing significant negative relationship with tot-P, total nitrogen, and chlorophyll A content and a positive relationship with lake transparency (Secchi depth). The concentration of these two heavy metals was thus higher in crayfish in the oligotrophic lakes and decreased linearly to the eutrophic ones. Pb was not related to any lake variable. Stable isotopes of carbon (delta C-13) and nitrogen (615N) in crayfish were a reflection of that found in the sediment as shown by positive linear relationships for the lakes. In the sediment of the lakes, delta C-13 signature showed significant negative relationships with the trophic indicators but positive results were shown for lake transparency. The trophic gradient of the lakes was reflected by delta C-13 in the sediment and in the crayfish. 615N in crayfish was a reflection of 615N in the sediment but the relationship was not coupled to the trophic statue of the lakes. The results from the study show that Cd and Hg in benthic omnivores as crayfish are affected by ecological processes in lakes, such as eutrophication. Stable isotopes, such as 13C and 15 N, can be used to study these ecological processes.
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